title: Anabolic steroids reduce spinal cord injury-related bone loss in rats associated with increased Wnt signaling.
abstract: BACKGROUND
  Spinal cord injury (SCI) causes severe bone loss. At present, there is no practical treatment to delay or prevent bone loss in individuals with motor-complete SCI. Hypogonadism is common in men after SCI and may exacerbate bone loss. The anabolic steroid nandrolone reduces bone loss due to microgravity or nerve transection.
  
  
  OBJECTIVE
  To determine whether nandrolone reduced bone loss after SCI and, if so, to explore the mechanisms of nandrolone action.
  
  
  METHODS
  Male rats with complete transection of the spinal cord were administered nandrolone combined with a physiological replacement dose of testosterone, or vehicle, beginning on day 29 after SCI and continued for 28 days.
  
  
  RESULTS
  SCI reduced distal femoral and proximal tibial bone mineral density (BMD) by 25 and 16%, respectively, at 56 days. This bone loss was attenuated by nandrolone. In ex vivo osteoclasts cultures, SCI increased mRNA levels for tartrate-resistant acid phosphatase (TRAP) and calcitonin receptor; nandrolone-normalized expression levels of these transcripts. In ex vivo osteoblast cultures, SCI increased receptor activator of NF-kB ligand (RANKL) mRNA levels but did not alter osteoprotegerin (OPG) mRNA expression; nandrolone-increased expression of OPG and OPG/RANKL ratio. SCI reduced mRNA levels of Wnt signaling-related genes Wnt3a, low-density lipoprotein receptor-related protein 5 (LRP5), Fzd5, Tcf7, and ectodermal-neural cortex 1 (ENC1) in osteoblasts, whereas nandrolone increased expression of each of these genes.
  
  
  CONCLUSIONS
  The results demonstrate that nandrolone reduces bone loss after SCI. A potential mechanism is suggested by our findings wherein nandrolone modulates genes for differentiation and activity of osteoclasts and osteoblasts, at least in part, through the activation of Wnt signaling.
authors.affiliation: Mount Sinai Bone Program, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.affiliation: Center of Excellence for the Medical Consequences of SCI, James J. Peters VA Medical Center, Bronx, NY, USA.
authors.forename: Jiangping
authors.initials: J
authors.lastname: Pan
authors.affiliation: Mount Sinai Bone Program, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Yuanzhen
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Center of Excellence for the Medical Consequences of SCI, James J. Peters VA Medical Center, Bronx, NY, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Mount Sinai Bone Program, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Jianghua
authors.initials: J
authors.lastname: Li
authors.affiliation: Mount Sinai Bone Program, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Xuan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Center of Excellence for the Medical Consequences of SCI, James J. Peters VA Medical Center, Bronx, NY, USA.
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Center of Excellence for the Medical Consequences of SCI, James J. Peters VA Medical Center, Bronx, NY, USA; Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA; and Department of Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Bauman
authors.affiliation: Center of Excellence for the Medical Consequences of SCI, James J. Peters VA Medical Center, Bronx, NY, USA; Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA; and Department of Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Cardozo
authors.affiliation: Mount Sinai Bone Program, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Mone
authors.initials: M
authors.lastname: Zaidi
authors.affiliation: Center of Excellence for the Medical Consequences of SCI, James J. Peters VA Medical Center, Bronx, NY, USA; and Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Weiping
authors.initials: W
authors.lastname: Qin
mesh_terms: D045930:Anabolic Agents / Q000494:pharmacology*; D000818:Animals; D001862:Bone Resorption / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D002454:Cell Differentiation / Q000187:drug effects; D004195:Disease Models, Animal; D008297:Male; D009277:Nandrolone / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D013119:Spinal Cord Injuries / Q000150:complications* / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: D045930:Anabolic Agents; D009277:Nandrolone